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ENGLISH ABSTRACT
汉族毛囊角化病一个家系的临床表型及遗传学分析
张士德
姜淼
林榕
金佳慧
赵敬军
作者及单位信息
·
DOI： 10.3760/cma.j.cn511374-20240908-00477
Analysis of clinical feature and genetic variant in a Chinese Han pedigree affected with Darier′s disease
Zhang Shide
Jiang Miao
Lin Rong
Jin Jiahui
Zhao Jingjun
Authors Info & Affiliations
Zhang Shide
Department of Dermatology, Fuding Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuding, Fujian 355200, China
Jiang Miao
Department of Dermatology, Tongji Hospital of Tongji University, Shanghai 200065, China
Lin Rong
Department of Laboratory Medicine, Fuding Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuding, Fujian 355200, China
Jin Jiahui
Department of Dermatology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Zhao Jingjun
Department of Dermatology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
·
DOI： 10.3760/cma.j.cn511374-20240908-00477
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摘要

目的探讨1个汉族毛囊角化病(DD)家系的临床表型与遗传学特征。

方法选取2023年10月22日就诊于同济大学附属同济医院的1个DD家系为研究对象。收集该家系临床资料，对先证者进行全基因组外显子测序，筛选可疑变异位点后对家系成员进行Sanger测序验证，并对变异位点进行生物信息学分析。本研究已通过同济大学附属同济医院医学伦理委员会的审查(批准号：K-W-2024-004)。

结果①先证者为67岁女性，具有DD临床特点如皮脂溢出部位角化性丘疹。②全基因组外显子测序显示先证者 ATP2A2基因第1外显子存在c.68G>A(p.Gly23Glu)错义变异；Sanger测序提示先证者长女同样携带该变异，家系其他成员未检测到该变异，提示该变异与家系疾病表型存在共分离现象。③参照美国医学遗传学与基因组学学会(ACMG)关于基因变异位点的解读原则，该变异被判定为致病性(PS1＋PM1＋PM2_Supporting＋PP1＋PP3＋PP4)。

结论 ATP2A2基因c.68G>A(p.Gly23Glu)变异可能是该家系的遗传学病因，进一步丰富了DD患者基因变异谱，为DD患者的临床诊断和遗传咨询提供了依据。

毛囊角化病; ATP2A2基因 ;基因变异
ABSTRACT

ObjectiveTo explore the clinical phenotype and genetic characteristics of a Chinese Han pedigree with Darier′s disease(DD).

MethodsA DD pedigree, who visited Tongji Hospital of Tongji University on October 22, 2023, was selected as the study subject. Clinical data of the pedigree were collected, and whole-genome exom sequencing was performed on the proband. Suspected variant loci were screened, and Sanger sequencing was used to validate the variant in pedigree members. Bioinformatics analysis was performed on the variant loci. This study was approved by the Medical Ethics Committee of Tongji Hospital of Tongji University(Ethics No.K-W-2024-004).

Results① The proband is a 67-year-old female with clinical features of DD, such as keratotic papules in sebaceous areas. ② Whole-genome exom sequencing revealed a missense variant, c. 68G>A (p.Gly23Glu), in the exon 1 of ATP2A2 gene of the proband. Sanger sequencing showed that the proband′s eldest daughter also carried this variant. This variant was not detected in other pedigree members, indicating a co-segregation of the variant with the disease phenotype in the pedigree. ③ According to the interpretation principles of gene variants by the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PS1+ PM1+ PM2_Supporting+ PP1+ PP3+ PP4).

ConclusionsThe c. 68G>A (p.Gly23Glu) variant in the ATP2A2 gene may be the genetic cause of the disease in this pedigree. This finding further enriches the genetic variant spectrum in DD patients and provides a basis for clinical diagnosis and genetic counseling for patients.

Darier′s disease; ATP2A2 gene ;Genetic variant
Zhao Jingjun, Email: mocdef.3ab61ocymoahz

△Zhang Shide and Jiang Miao contributed equally to this work

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引用本文

张士德,姜淼,林榕,等. 汉族毛囊角化病一个家系的临床表型及遗传学分析[J]. 中华医学遗传学杂志,2025,42(02)：206-211.

DOI:10.3760/cma.j.cn511374-20240908-00477

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毛囊角化病(Darier′s disease，DD)(OMIM 124200)是一种具有临床和遗传异质性的罕见遗传性皮肤疾病，呈常染色体显性遗传模式，以表皮细胞角化不良为重要特征。DD的典型临床表现为皮脂溢出部位多发的、角化性、油腻性丘疹甚至斑块，可伴有掌跖角化性点状凹陷及甲改变(甲下角化过度增生、甲营养不良、甲萎缩等) [ 1 ]。DD的致病基因为定位于12q23-q24.1区间上的 ATP2A2基因，但其基因型与临床表型的相关性尚不明确 [ 2 ]。本研究收集了1个中国汉族DD家系的详细临床资料，并对先证者及其表型正常的家系成员进行了 ATP2A2基因的变异研究，以加强对该病的认识，为家系遗传咨询提供依据。现将研究结果报道如下。
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备注信息
A
赵敬军，Email： mocdef.3ab61ocymoahz
B

△张士德和姜淼对本文有同等贡献

C

张士德：酝酿和设计实验、实施实验、采集数据、分析并解释数据、起草并撰写文章；姜淼：酝酿和设计实验、分析和解释数据、对文章的知识性内容作批判性审阅、获取研究经费；林榕：采集数据、分析并解释数据、技术支持；金佳慧：分析并解释数据、技术支持；赵敬军：酝酿和设计实验、实施研究、对文章的知识性内容作批判性审阅、获取研究经费、行政、技术或材料支持、指导、支持性贡献

D
所有作者均声明不存在利益冲突
E
国家自然科学基金 (82072258，82373482)
上海市卫健委临床研究项目 (202240346)
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